Amidins and Imidates as Transient Directing Groups in C-H-activating Reactions

在本研究计画中，我们想要发展一种在碳氢活化条件下，酚类与苯胺类的直接邻炔基化反应。为此，我们希望建立脒和亚胺作为新的瞬态导向基团（tdGs）的炔基化反应。根据定义，tdG是在C-H活化转化期间安装的，以便更好地引导过渡金属形成所需的C-H键，最后在成功官能化后将其裂解。为了保证在这种特定情况下tdG形成的可逆性，我们希望引入邻-X-H-酸性芳族腈作为其前体。在第一个目标中，我们希望合成各种这样的贫电子邻-X-H-酸性腈，并通过与精心选择的苯胺和苯酚直接反应将它们转化为脒和亚胺酯。我们想从机理上研究这个重要的反应，特别是它的可逆性。由于脒基和亚胺基在C-H-活化炔基化反应中还没有被描述，因此在它们的指导下的定向炔基化反应应该被建立为“经典的”定向基团。将使用炔基（芳基）苯并碘多烯酮作为亲电炔源。这些试剂已被用于各种引导的C-H-活化反应，因为它们显示出显着的高反应性，同时它们是工作台稳定的，易于处理。除了直接的邻炔基化，我们还希望开发多米诺骨牌式的方法来有效地获得各种高度取代的杂环。根据我们从关于脒和亚氨酸酯形成的可逆性的初始机理研究和从炔基化反应获得的信息，我们最终应该能够开发出仅使用催化量的邻-C-H-酸性腈的方法。在这里，脒和亚酰胺作为tdG原位生成。此外，我们想研究这种转化的区域和化学选择性，我们希望能够合理地控制这种选择性。

In this research project we want to develop a direct ortho-alkynylation of phenols and anilins under C-H-activating conditions. For this purpose, we want to establish amidines and imidates as novel transient directing groups (tdGs) for alkynylation reactions. By definition, tdGs are installed during the C-H-activating transformation for a better guidance of the transition metal to the desired C-H-bond and finally they are cleaved after a successful functionalization. To guarantee the reversibility of the tdG formation in this specific case, we want to introduce ortho-X-H-acidic aromatic nitriles as their precursors. In a first goal we want to synthesize a variety of such electron poor ortho-X-H-acidic nitriles und transform them into amidines and imidates by direct reaction with well-chosen anilines and phenols. We want to study this important reaction mechanistically, in particular its reversibility. Since amidines as well as imidates have not been described so far in C-H-activating alkynylations, a directed alkynylation under their guidance as “classical” directing group should be established. As electrophilic alkyne source alkynyl(aryl)benziodoxolones will be used. These reagents have been used in a variety of guided C-H-activating reactions since they show a remarkable high reactivity and at the same time they are bench stable and easy to handle. Besides the direct ortho-alkynylation, we want to develop domino-type processes to get an efficient access to a variety of highly substituted heterocycles. From the information that we gained from the initial mechanistic studies regarding the reversibility of the amidine and imidate formation and from the alkynylation reactions, we finally should be able to develop a process that only uses catalytic amounts of the ortho-C-H-acidic nitrile. Here the amidines and imidates are generated in situ as tdGs. In addition, we want to study the regio- and chemoselectivity of this transformation and we want to be able to rationally steer this selectivity.